A Study to Assess the Pharmacokinetics of Ceftaroline in End Stage Renal Disease Patients and Matched Healthy Subjects - Full Text View

Purpose

The purpose of this study is to assess the safety, tolerability and pharmacokinetics of Ceftaroline in a group of patients with renal disease and matching healthy subjects with normal renal function

Condition	Intervention	Phase
Renal Disease	Drug: 200 mg Ceftaroline fosamil Drug: 600 mg Ceftaroline fosamil	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Basic Science
Official Title:	An Open-label, Nonrandomised, Phase I Study to Assess the Pharmacokinetics of Ceftaroline After Intravenous Administration of aSingle Dose of Ceftaroline Fosamil (200 mg) to Patients With End-stage Renal Disease Undergoing Haemodialysis When Compared to a Single Dose of Ceftaroline Fosamil (600 mg)

Resource links provided by NLM:

MedlinePlus related topics: Kidney Failure

Drug Information available for: Ceftaroline Ceftaroline fosamil

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

Pharmacokinetics of Ceftaroline after intravenous infusion of Ceftaroline Fosamil in patients with end-stage renal disease and a matched control population with normal renal function to characterise the clearance of Ceftaroline. [ Time Frame: pre-dose, 20, 40, 60, 65, 75, 90 min, 2.25, 3.25 , 4.25, 5.25, 8, 12, 24, 36, 48 h ] [ Designated as safety issue: No ]
Group 1 (patient group/period 1 and 2); Group 2 (control group - healthy). Maximum plasma concentration (Cmax), time to maximum concentration (tmax), area under the plasma concentration-time curve from zero to infinity (AUC), area under the plasma concentration-time curve from zero to time of the last quantifiable concentration (AUC(0-t)), area under the plasma concentration-time curve from zero to 12 hours after the start of the infusion (AUC(0-12)), terminal rate constant (λz), terminal half-life (t1/2λz),dose normalised Cmax, dose-normalised AUC, dose-normalised AUC(0-t), and dose-normalised AUC(0-12)
Pharmacokinetics of Ceftaroline after intravenous infusion of Ceftaroline fosamil in patients with end-stage renal disease and a matched control population with normal renal function to characterise the clearance of Ceftaroline. [ Time Frame: pre-dose, 20, 40, 60, 65, 75, 90 min, 2.25, 3.25 , 4.25, 5.25, 8, 12, 24, 36, 48 h ] [ Designated as safety issue: No ]
Group 1 (patient group/period 1 and 2);Group 2 (control group - healthy). Mean residence time (MRT), total body clearance of drug from plasma (CL for ceftaroline fosamil, apparent CL for ceftaroline), volume of distribution based on the terminal phase (Vz for ceftaroline fosamil, apparent Vz for ceftaroline), volume of distribution at steady-state (Vss for ceftaroline fosamil, apparent Vss for ceftaroline)
Pharmacokinetics of Ceftaroline after intravenous infusion of Ceftaroline fosamil in patients with end stage renal diseaseand to characterise the clearance of Ceftaroline. [ Time Frame: pre-dose, 20, 40, 60, 65, 75, 90 min, 2.25, 3.25 , 4.25, 5.25, 8, 12, 24, 36, 48 h ] [ Designated as safety issue: No ]
Group 1 (patient group/period 2). Area under the plasma concentration -time curve from 75 min to 5.25 hr after the start of the infusion (AUC(1-5)), amount of drug extracted unchanged into the dialysate (AD) during each 1-hour interval, cumulatively, and overall (AD(1-5)) for the entire haemodialysis session (time: 75 min to 5.25 hr after the start of infusion); percent of dose recovered in dialysate (fD,%) during each 1-hour interval, cumulatively, and overall (fD(1-5),%) for the entire haemodialysis session (time: 75 min to 5.25 hr after the start of infusion), extraction coefficient (E) at each time point during haemodialysis

Secondary Outcome Measures:

Safety and tolerability in terms of adverse events, laboratory data, physical examinations, ECG and vital signs. [ Time Frame: Screening up to 10 days after discharge from study site. ] [ Designated as safety issue: Yes ]
Pharmacokinetics of Ceftaroline M-1 after intravenous infusion of Ceftaroline fosamil in patients with end-stage renal disease and a matched control population with normal renal function to characterise the clearance of Ceftaroline. [ Time Frame: pre-dose, 20, 40, 60, 65, 75, 90 min, 2.25, 3.25 , 4.25, 5.25, 8, 12, 24, 36, 48 h ] [ Designated as safety issue: No ]
Group 1 (patient group/period 1 and 2); Group 2 (control group - healthy). Maximum plasma concentration (Cmax), time to maximum concentration (tmax), area under the plasma concentration-time curve from zero to infinity (AUC), area under the plasma concentration-time curve from zero to time of the last quantifiable concentration (AUC(0-t)), area under the plasma concentration-time curve from zero to 12 hours after the start of the infusion (AUC(0-12)), terminal rate constant (λz), terminal half-life (t1/2λz),dose normalised Cmax, dose-normalised AUC, dose-normalised AUC(0-t), and dose-normalised AUC(0-12)
Pharmacokinetics of Ceftaroline M-1 after intravenous infusion of Ceftaroline fosamil in patients with end stage renal disease and to characterise the clearance of Ceftaroline. [ Time Frame: pre-dose, 20, 40, 60, 65, 75, 90 min, 2.25, 3.25 , 4.25, 5.25, 8, 12, 24, 36, 48 h ] [ Designated as safety issue: No ]
Group 1 (patient group/period 2). Area under the plasma concentration -time curve from 75 min to 5.25 hr after the start of the infusion (AUC(1-5)), amount of drug extracted unchanged into the dialysate (AD) during each 1-hour interval, cumulatively, and overall (AD(1-5)) for the entire haemodialysis session (time: 75 min to 5.25 hr after the start of infusion); percent of dose recovered in dialysate (fD,%) during each 1-hour interval, cumulatively, and overall (fD(1-5),%) for the entire haemodialysis session (time: 75 min to 5.25 hr after the start of infusion), extraction coefficient (E) at each time point during haemodialysis
Pharmacokinetics of Ceftaroline fosamil after intravenous infusion of Ceftaroline fosamil in patients with end-stage renal disease and a matched control population with normal renal function to characterise the clearance of Ceftaroline. [ Time Frame: pre-dose, 20, 40, 60, 65, 75, 90 min, 2.25, 3.25 , 4.25, 5.25, 8, 12, 24, 36, 48 h ] [ Designated as safety issue: No ]
Group 1 (patient group/period 1 and 2); Group 2 (control group - healthy). Maximum plasma concentration (Cmax), time to maximum concentration (tmax), area under the plasma concentration-time curve from zero to infinity (AUC), area under the plasma concentration-time curve from zero to time of the last quantifiable concentration (AUC(0-t)), area under the plasma concentration-time curve from zero to 12 hours after the start of the infusion (AUC(0-12)), terminal rate constant (λz), terminal half-life (t1/2λz),dose normalised Cmax, dose-normalised AUC, dose-normalised AUC(0-t), and dose-normalised AUC(0-12)
Pharmacokinetics of Ceftaroline fosamil after intravenous infusion of Ceftaroline fosamil in patients with end-stage renal disease and a matched control population with normal renal function to characterise the clearance of Ceftaroline. [ Time Frame: pre-dose, 20, 40, 60, 65, 75, 90 min, 2.25, 3.25 , 4.25, 5.25, 8, 12, 24, 36, 48 h ] [ Designated as safety issue: No ]
Group 1 (patient group/period 1 and 2);Group 2 (control group - healthy). Mean residence time (MRT), total body clearance of drug from plasma (CL for ceftaroline fosamil, apparent CL for ceftaroline), volume of distribution based on the terminal phase (Vz for ceftaroline fosamil, apparent Vz for ceftaroline), volume of distribution at steady-state (Vss for ceftaroline fosamil, apparent Vss for ceftaroline).

Estimated Enrollment:	16
Study Start Date:	February 2013
Estimated Study Completion Date:	October 2013
Estimated Primary Completion Date:	October 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: AZ drug: A 200 mg Ceftaroline fosamil 1h infusion	Drug: 200 mg Ceftaroline fosamil 1 h infusion
Experimental: AZ drug: B 600 mg Ceftaroline fosamil 1h infusion	Drug: 600 mg Ceftaroline fosamil 1 h infusion

Detailed Description:

An Open-label, Nonrandomised, Phase I Study to Assess the Pharmacokinetics of Ceftaroline After Intravenous Administration of aSingle Dose of Ceftaroline Fosamil (200 mg) to Patients with End-stage Renal Disease Undergoing Haemodialysis when Compared to a Single Dose of Ceftaroline Fosamil (600 mg)

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion criteria:

Provision of signed and dated, written informed consent prior to any study specific procedures
Male and female subjects aged 18 to 75 years (inclusive) with suitable veins for cannulation or repeated venipuncture
Women of childbearing potential must have a negative pregnancy test, be non-lactating, and be using a highly effective form of birth control for 3 months prior to enrollment, during the study, and for 3 months after completion of all study-related proceed
Have a body mass index (BMI) between 18 and 35 kg/m2 and weigh at between 50 and 100 kg
Haematocrit level higher than 30% at screening and baseline for each treatment period

Exclusion criteria:

History or presence of gastrointestinal, hepatic, or any other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs
Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results, as judged by the investigator
Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG that may interfere with the interpretation of QTc interval changes
History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study
Receiving any dialysis treatment other than intermittent haemodialysis

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01664065

Contacts

Contact: Quintiles Drug Research Unit Call Centre

0800 634 1132

Locations

United Kingdom
	Recruiting
London, United Kingdom

Sponsors and Collaborators

AstraZeneca

Investigators

Study Director:	David Melnick, MD	AstraZeneca Pharmaceuticals;C2C-716 1800 Concord PikePO. Box 15437Wilmington De 19850-5437
Principal Investigator:	Arpeat Kaviya, MBChB, MRCP	Quintiles Drug Research Unit at Guy's Hospital 6 Newcomen St
Study Chair:	Mirjana Kujacic, MD	AstraZeneca Research and Development SE-431 83 Mölndal

More Information

No publications provided

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT01664065 History of Changes
Other Study ID Numbers:	D3720C00012
Study First Received:	August 10, 2012
Last Updated:	April 29, 2013
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by AstraZeneca:

Patient Safety
Tolerability
Pharmacokinetics

Additional relevant MeSH terms:

Kidney Diseases
Kidney Failure, Chronic
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency

ClinicalTrials.gov processed this record on June 17, 2013